Oncoinvent - Q2

17.10.2018 kl 11:14 974

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Limer inn abstractet under:

Alpha-Emitting Radiopharmaceutical for IP Therapy of
Peritoneal Metastases: In Vitro Evaluation and Therapeutic
Effects in a Murine Model
T. B. Bønsdorff1, E. Napoli1,2,3, I. S. Jorstad1, S. Westrøm1,2,3, Ø.
S. Bruland3,2,1, R. H. Larsen4; 1Oncoinvent AS, Oslo, NORWAY,
2University of Oslo, Oslo, NORWAY, 3The Norwegian Radium
Hospital, Oslo University Hospital, Oslo, NORWAY, 4Sciencons AS,
Purpose: Radium-224 (224Ra) labeled calcium carbonate
(CaCO3) microparticles have been developed with the intent
to treat micrometastases located in the abdominal cavity. The
microparticles act as carriers for the α-emitter 224Ra and ensure
high intraperitoneal (IP) retention of the radioactivity without
cellular targeting. This novel α- therapy has a short action range
in tissue and is designed to confine the radiation exposure to
the IP cavity, treating both linings of the peritoneal surfaces as
well as liquid volumes. The retention of radioactivity adsorbed
on the surface of CaCO3 microparticles was examined in vitro
and in vivo. Therapeutic efficacy of the 224Ra-microparticles was
evaluated in a murine xenograft of an ascites presenting human
cell line. Materials and Methods: The retention of 224Ra and its
daughter 212Pb adsorbed on different amounts of CaCO3 microparticles
was evaluated over time both in vitro and in vivo.
Immunodeficient athymic nude mice were used for the in vivo
studies. For investigation of therapeutic effect, mice inoculated
IP with human ovarian cancer cells ES-2 were used. The ES-2 cell
line causes aggressive development of ascites. Varying amounts
of 224Ra-microparticles were administered IP (5-25 mg) with 10-
25 kBq total activity per mice. The treatment was injected the
day after cell inoculation. Survival was assessed. Results: The
retention of 224Ra and its daughter 212Pb on CaCO3 microparticles
increased with increasing amounts of microparticles. This was
observed both in vitro and in biodistribution studies in mice. The
survival studies showed that free cationic 224Ra (given as 224RaCl2
solution) had a therapeutic index (ratio of median survival of
treated mice versus control) of 1.8, whereas administration of
224Ra-labeled CaCO3 microparticles gave a therapeutic index (TI)
up to 2.8. No strong correlation between microparticle amount
and effect on survival in mice with IP xenografts were observed,
at the microparticle amounts tested. The highest amount (25
mg per mice) however, showed inferior survival (TI of 1.7). Conclusion:
Efficient 224Ra-labeling of CaCO3 microparticles was
achieved, with high retention of the radionuclide on the particles
both in vitro and in vivo. Therapeutic studies showed superior
survival when treating with IP injection of 224Ra-CaCO3 microparticle
suspension compared to IP injection of free cationic
224Ra solution. The data also indicate that high concentrations
of particles may potentially reduce the antitumor activity of the